Gene therapy

Patients suffering from a rare congenital liver disease could be cured with a technique that delivers gene therapy directly to the organ.

The method, being studied by Philips Research and GlyGenix Therapeutics, would use microscopic bubbles to penetrate liver cells so that therapeutic DNA can enter.

Such a technique could be used to treat patients with Glycogen Storage Disease Type 1a (GSD-1a).

Those with the inherited disease carry a defective G6Pase gene that prevents the body from producing an enzyme that plays a critical role in the conversion of glycogen to glucose. The result means a patient’s liver stores excessive amounts of glycogen.

Philips and GlyGenix Therapeutics believe that these patients could one day have microbubbles and a non-defective G6Pase gene injected into their bloodstream.

The microbubbles, which are gas-filled spheres made of biocompatible material, act as an ultrasound contrast agent. Their arrival in the liver would be tracked with an ultrasound scanner.

When at the liver, a doctor would subject the microbubbles to high-energy focused ultrasound pulses at their resonant frequency, causing them to rapidly expand and contract.

Hans Hofstraat, vice-president of Philips Research for healthcare strategic partnerships, said: ‘The function of the ultrasound is to invoke sonoporation to open up the tissue and the cells so the genetic material can enter.’

Philips and GlyGenix Therapeutics are conducting pre-clinical studies into this therapy with collaboration from the Division of Medical Genetics at Duke University, North Carolina, which manages the treatment of GSD-1a patients.

Hofstraat said the Philips and GlyGenix Therapeutics team will begin research with in-vitro systems in test tubes. The researchers will observe whether they can get their gene into a liver cell. If successful, the cell will produce an enzyme.

He added: ‘When we have determined what experimental conditions are needed to open up the cells, the next step will be to try this out in animal models.’

It is then hoped that the collaboration with Duke will make it easier to move from pre-clinical to clinical trials. However, Hofstraat would not speculate as to how far away that could be.